Research Spotlight

Haskins, I. N., J. W. Fleshman, R. L. Amdur and S. Agarwal (2016). “The impact of bowel preparation on the severity of anastomotic leak in colon cancer patients.” J Surg Oncol: 2016 Sep [Epub ahead of print].

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BACKGROUND AND OBJECTIVES: The routine use of preoperative bowel preparation (BP) is heavily debated in the colorectal surgery literature. To date, no study has investigated the effect preoperative BP has on patients with an established anastomotic leak. We therefore seek to compare the severity of patient morbidity and mortality in patients with a known anastomotic leak based on type of preoperative BP using the Targeted Colectomy American College of Surgeons National Surgery Quality Improvement Program (ACS-NSQIP). METHODS: All elective colon cancer operations performed with primary anastomosis were identified within the targeted colectomy database from 2012 to 2013. Patients who experienced a postoperative anastomotic leak were identified and stratified based on preoperative BP. Variables that had an association with mechanical BP at P < 0.10 were included in a multivariate logistic regression model to determine if BP was independently associated with postoperative morbidity and mortality. RESULTS: A total of 6,297 patients underwent elective colon resection with primary anastomosis for colon cancer. Two hundred and nineteen (3.5%) patients experienced an anastomotic leak. Thirty-day wound morbidity and mortality was not worse in patients who underwent preoperative BP. CONCLUSIONS: BP is not associated with worse patients outcomes in those patients with an established anastomotic leak following elective colon research with primary anastomosis.

Ramey, S. J., M. C. Abramowitz, D. Moghanaki, S. Agrawal, J. A. Efstathiou, T. M. Pisansky, J. M. Michalski, B. F. Koontz, D. A. Hamstra, F. Y. Feng, S. Liauw, M. S. Anscher, A. Pollack, R. B. Den, K. L. Stephans, M. Kattan, T. Gao, A. J. Stephenson and R. D. Tendulkar (2016). “Benefit of elective nodal irradiation and androgen deprivation therapy with postprostatectomy salvage radiation therapy for prostate cancer.” Int J Radiat Oncol Biol Phys 96(2s): S102.

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Salvage radiation therapy (SRT) has resulted in improved outcomes for patients (pts) with a detectable PSA post-prostatectomy. However, the optimal treatment strategy remains controversial regarding whether to treat with elective pelvic lymph node irradiation (WPRT) versus only the prostate bed (PB-RT) and whether to offer androgen deprivation therapy (ADT). Therefore, a multi-institutional database was analyzed to determine the association of WPRT and PB-RT with or without ADT on freedom from biochemical failure (FFBF) and freedom from distant metastases (FFDM) after SRT.

Rossignol, P., M. Legrand, M. Kosiborod, S. M. Hollenberg, W. F. Peacock, M. Emmett, M. Epstein, C. P. Kovesdy, M. B. Yilmaz, W. G. Stough, E. Gayat, B. Pitt, F. Zannad and A. Mebazaa (2016). “Emergency management of severe hyperkalemia: Guideline for best practice and opportunities for the future.” Pharmacol Res 113(Pt A): 585-591.

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Hyperkalemia is a common electrolyte disorder, especially in chronic kidney disease, diabetes mellitus, or heart failure. Hyperkalemia can lead to potentially fatal cardiac dysrhythmias, and it is associated with increased mortality. Determining whether emergency therapy is warranted is largely based on subjective clinical judgment. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT) aimed to evaluate the current knowledge pertaining to the emergency treatment of hyperkalemia. The INI-CRCT developed a treatment algorithm reflecting expert opinion of best practices in the context of current evidence, identified gaps in knowledge, and set priorities for future research. We searched PubMed (to August 4, 2015) for consensus guidelines, reviews, randomized clinical trials, and observational studies, limited to English language but not by publication date. Treatment approaches are based on small studies, anecdotal experience, and traditional practice patterns. The safety and real-world effectiveness of standard therapies remain unproven. Prospective research is needed and should include studies to better characterize the population, define the serum potassium thresholds where life-threatening arrhythmias are imminent, assess the potassium and electrocardiogram response to standard interventions. Randomized, controlled trials are needed to test the safety and efficacy of new potassium binders for the emergency treatment of severe hyperkalemia in hemodynamically stable patients. Existing emergency treatments for severe hyperkalemia are not supported by a compelling body of evidence, and they are used inconsistently across institutions, with potentially significant associated side effects. Further research is needed to fill knowledge gaps, and definitive clinical trials are needed to better define optimal management strategies, and ultimately to improve outcomes in these patients.

Salam, S., R. Kotloff, P. Garcha, S. Krishnan, D. Joshi, P. Grady and A. Duggal (2016). “Lung transplanation after 125 days on ecmo for severe refractory hypoxemia with no prior lung disease.” Asaio j: 2016 Sep [Epub ahead of print].

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Veno-venous extracorporeal membrane oxygenation (ECMO) has become a viable and increasingly utilized option for the treatment of refractory hypoxemia in severe acute respiratory distress syndrome (ARDS). However, options are limited for ARDS patients who fail to wean from ECMO. The high rates of infection, presence of extrapulmonary end organ damage, ICU-acquired weakness, and high short-term mortality associated with ARDS are all significant hurdles that make lung transplantation a difficult prospect to consider. However, ECMO support has been used as a bridge to transplant in patients with other underlying chronic lung diseases. Our case illustrates the successful use of lung transplantation for a patient with no previous lung disease who developed refractory ARDS requiring protracted ECMO support. The use of ambulatory ECMO with early institution of physical therapy is an essential component in preparing such patients for successful transplantation.

Sarantopoulos, J., S. Goel, V. Chung, P. Munster, S. Pant, M. R. Patel, J. Infante, H. Tawbi, C. Becerra, J. Bruce, F. Kabbinavar, A. C. Lockhart, E. Tan, S. Yang, G. Carlson, J. W. Scott and S. Sharma (2016). “Randomized phase 1 crossover study assessing the bioequivalence of capsule and tablet formulations of dovitinib (tki258) in patients with advanced solid tumors.” Cancer Chemother Pharmacol: 2016 Sep [Epub ahead of print].

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PURPOSE: A capsule formulation of the tyrosine kinase inhibitor dovitinib (TKI258) was recently studied in a phase 3 renal cell carcinoma trial; however, tablets are the planned commercial formulation. Therefore, this randomized 2-way crossover study evaluated the bioequivalence of dovitinib tablet and capsule formulations in pretreated patients with advanced solid tumors, excluding breast cancer. METHODS: In this 2-part study, eligible patients received dovitinib 500 mg once daily on a 5-days-on/2-days-off schedule. During the 2-period bioequivalence phase, patients received their initial formulation (capsule or tablet) for 3 weeks before being switched to the alternative formulation in the second period. Patients could continue to receive dovitinib capsules on the same dosing schedule during the post-bioequivalence phase. RESULTS: A total of 173 patients were enrolled into the bioequivalence phase of the study (capsule –> tablet, n = 88; tablet –> capsule, n = 85), and 69 patients had evaluable pharmacokinetics (PK) for both periods. PK analyses showed similar exposure and PK profiles for the dovitinib capsule and tablet formulations and supported bioequivalence [geometric mean ratios: AUClast, 0.95 (90 % CI 0.88-1.01); C max, 0.98 (90 % CI 0.91-1.05)]. The most common adverse events, suspected to be study drug related, included diarrhea (60 %), nausea (53 %), fatigue (45 %), and vomiting (43 %). Of 168 patients evaluable for response, 1 achieved a partial response, and stable disease was observed in 32 % of patients. CONCLUSIONS: Dovitinib capsules and tablets were bioequivalent, with a safety profile similar to that observed in other dovitinib studies of patients with heavily pretreated advanced solid tumors.